Borden Lacy & Shannon Kordus - VI4 Scientists Doing Things
Denis Mogilenko, PhD
- PhD: Institute for Experimental Medicine, Saint Petersburg, Russia
- Postdoctoral Fellow: French Institute of Health and Medical Research (INSERM)
- Postdoctoral Fellow: Washington University School of Medicine in St. Louis
Our research focuses on how obesity and aging reshape immune responses and lead to inflammatory diseases. Immune cells are sensitive to their metabolic environment, which affects intracellular metabolism and signaling and fine-tune immune functions. We are interested in understanding how metabolic cues regulate communication between immune cells, focusing on dendritic cells and T cells. Our Lab studies how obesity and aging disturb the immune and metabolic balance and lead to excessive inflammation, including diseases such as psoriasis and asthma. We decode molecular mechanisms that link dendritic cell metabolism to tissue inflammation by combining mouse models of inflammatory skin and lung diseases with systems immunology approaches.
Publications on
Select Publications:
Mogilenko DA*, Shchukina I*, Artyomov MN. Immune ageing at single-cell resolution. Nat Rev Immunol 22, 484–498 (2022). https://doi.org/10.1038/s41577-021-00646-4 (*co-first authors)
Mogilenko DA, Shpynov O, Andhey PS, Arthur L, Swain A, Esaulova E, Brioschi S, Shchukina I, Kerndl M, Bambouskova M, Yao Z, Laha A, Zaitsev K, Burdess S, Gillfilan S, Stewart SA, Colonna M, Artyomov MN. Comprehensive profiling of an aging immune system reveals clonal GZMK+ CD8 T cells as conserved hallmark of inflammaging. Immunity 54(1):99-115.e12 (2021). https://doi.org/10.1016/j.immuni.2020.11.005
Brioschi S*, Wang W-L*, Peng V*, Wang M, Shchukina I, Greenberg ZJ, Bando JK, Jaeger N, Czepielewski RS, Swain A, Mogilenko DA, Beatty WL, Bayguinov P, Fitzpatrick JAJ, Schuettpelz LG, Fronick CC, Smirnov I, Kipnis J, Shapiro VS, Wu GF, Gilfillan S, Cella M, Artyomov MN, Kleinstein SH, Colonna M. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science 373(6553):eabf9277 (2021). https://www.science.org/doi/10.1126/science.abf9277 (*co-first authors)
Arthur L*, Esaulova E*, Mogilenko DA, Tsurinov P, Burdess S, Laha A, Presti R, Goetz B, Watson MA, Goss CW, Gurnett CA, Mudd PA, Beers C, O’Halloran JA & Artyomov MN. Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging. Nature Aging 1, 535-549 (2021). https://doi.org/10.1038/s43587-021-00067-x (*co-first authors)
Bambouskova M, Potuckova L, Paulenda T, Kerndl M, Mogilenko DA, Lizotte K, Swain A, Hayes S, Sheldon RD, Kim H, Kapadnis U, Ellis AE, Isaguirre C, Burdess S, Laha A, Amarasinghe GK, Chubukov V, Roddy TP, Diamond MS; Jones RJ, Simons DM, Artyomov MN. Itaconate confers tolerance to late inflammasome activation. Cell Reports 34(10):108756 (2021). https://doi.org/10.1016/j.celrep.2021.108756
Mogilenko DA, Haas JT, L'homme L, Fleury S, Quemener S, Levavasseur M, Becquart C, Wartelle J, Bogomolova A, Pineau L, Molendi-Coste O, Lancel S, Dehondt H, Gheeraert C, Melchior A, Dewas C, Nikitin A, Pic S, Rabhi N, Annicotte JS, Oyadomari S, Velasco-Hernandez T, Cammenga J, Foretz M, Viollet B, Vukovic M, Villacreces A, Kranc K, Carmeliet P, Marot G, Boulter A, Tavernier S, Berod L, Longhi MP, Paget C, Janssens S, Staumont-Sallé D, Aksoy E, Staels B, Dombrowicz D. Metabolic and innate immune cues merge into a specific inflammatory response via the UPR. Cell 177(5):1201-1216 (2019). https://doi.org/10.1016/j.cell.2019.03.018
Haas JT*, Vonghia L*, Mogilenko DA*, Verrijken A, Molendi-Coste O, Fleury S, Deprince A, Nikitin A, Woitrain E, Ducrocq-Geoffroy L, Pic S, Derudas B, Dehondt H, Gheeraert C, Van Gaal L, Driessen A, Lefebvre P, Staels B, Francque S, Dombrowicz D. Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution. Nature Metabolism 1(6):604-614 (2019). https://doi.org/10.1038/s42255-019-0076-1 (*co-first authors)
Devos M*, Mogilenko DA*, Fleury S, Gilbert B, Becquart C, Quemener S, Dehondt H, Tougaard P, Staels B, Bachert C, Vandenabeele P, Van Loo G, Staumont-Salle D, Declercq W, Dombrowicz D. Keratinocyte expression of A20/TNFAIP3 controls skin inflammation associated with atopic dermatitis and psoriasis. J Invest Dermatol 139(1):135-145 (2019). https://doi.org/10.1016/j.jid.2018.06.191 (*co-first authors)
Immunometabolism in obesity and aging
Monkeypox – symptoms, transmission, and prevention
Kelly E. Dooley, MD, PhD, MPH
Kelly Dooley, MD, PhD, MPH, is a Professor of Medicine, and Director of the Division of Infectious Disease within the Department of Medicine at Vanderbilt University Medical Center (VUMC).
As an infectious disease specialist and clinical pharmacologist, Dr. Dooley maintains an active clinical practice in HIV care. Her research focuses on tuberculosis therapeutics with an emphasis on clinical trials of TB drugs and HIV/TB co-treatment, as well as clinical pharmacology of TB and HIV drugs. She is lead investigator for trials of therapeutics for drug-sensitive and drug-resistant TB, TB-HIV, and pediatric TB meningitis. She is on the TB scientific committees of the AIDS Clinical Trials Group and IMPAACT networks, and is a consultant to World Health Organization on TB therapeutics and pharmacology.
Dr. Dooley earned her Master of Public Health in Epidemiology from University of North Carolina at Chapel Hill, and her medical degree from Duke University. She completed her Internal Medicine residency, and fellowships in Infectious Diseases and Clinical Pharmacology at Johns Hopkins University. She subsequently earned a PhD in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health. She joined VUMC in 2022, and is board certified in internal medicine and infectious diseases.
Rifat, D; Prideaux, B; Savic, RM; Urbanowski, ME; Parsons, TL; Luna, B; Marzinke, MA; Ordonez, AA; Demarco, VP; Jain, SK; Dartois, V; Bishai, WR; Dooley, KE. Using rabbits with cavitary disease and translational PK/PD modeling to understand TB trial results. Science Translational Medicine (2018) 10: eaai7786. PMC5969904.
Dooley, KE; Miyahara, S; von Groote-Biglingmaier, F; Sun, X; Hafner, R; Rosenkranz, SL; Ignatius, EH; Nuermberger, EL; Moran, L; Donahue, K; Swindells, S; Vanker, N; Diacon, AH; and the A5312 Study Team. Early Bactericidal Activity of Different Isoniazid Doses for Drug Resistant TB (INHindsight): A Randomized Open-label Clinical Trial. American Journal of Respiratory and Critical Care Medicine (2020) 201: 1579-1580.
Dooley KE, Rosenkranz SL, Conradie F, Moran L, Hafner R, von Groote-Bidlingmaier F, Lama J, Shenje J, de los Rios J, Comins K, Morganroth J, Diacon A, Cramer YS, Donahue K, Maartens G, and the AIDS Clinical Trials Group (ACTG) A5343 DELIBERATE Study Team. QT effects of bedaquiline, delamanid or both in patients with rifampicin–resistant TB: a randomized controlled trial. Lancet Inf Dis, (2021) 21: 975-983
Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV et al. ACTG/TBTC. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. New England Journal of Medicine, (2021) 384: 1705-1718.
Svensson, EM; Aweeka , F; Park, J-G; Marzan, F; Dooley, KE*§; Karlsson, MO* Model-based estimates of the effects of efavirenz on bedaquiline pharmacokinetics and suggested dose adjustments for patients co-infected with HIV and tuberculosis. Antimicrobial Agents and Chemotherapy (2013) 57: 2780-2787. PMC3716161.
Dooley, KE; Luetkemeyer, AF; Park, J-G; Allen, R; Cramer, Y; Murray, S; Sutherland, D; Aweeka, F; Koletar, SL; Marzan, F; Bao, J; Savic R; Haas, DW; ACTG A5306 Study Team. Phase I safety, PK, and pharmacogenetics study of the anti-TB drug PA-824 with concomitant lopinavir/ritonavir, efavirenz, or rifampin. Antimicrobial Agents Chemotherapy (2015) 58: 5245-52. PMC4135849.
Dooley, KE; Kaplan, R; Mwelase, N; Grinsztejn, B; Ticona, E; Lacerda, M; Sued, O; Belonosova, E; Ait-Khaled, M; Angelis, K; Brown, D; Singh, R; Talarico, CL; Tenorio, AR; Keegan, MR; Aboud, M; and the INSPIRING study group. Dolutegravir-based antiretroviral therapy for patients co-infected with tuberculosis and HIV: a multicenter, noncomparative, open-label, randomized trial. Clin Inf Diseases 2020; 70(4):549-556.
Dooley, KE; Savic, R; Gupte, A; Marzinke, MA; Zhang, N; Edward, VA; Wolf, L; Sebe, M; Likoti, J; Fyvie, MJ; Shibambo, I; Beattie, T; Chaisson, RE; Churchyard, GJ; DOLPHIN Study Team. Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients withHIV taking dolutegravir-based antiretroviral therapy: a phase I/II trial. Lancet HIV 2020. 7: e401-e409
Dooley, KE; Denti, P; Martinson, N; Cohn, S; Mashabela, F; Hoffmann, J; Haas, DW, Hull, J; Msandiwa, R; Castel, S; Wiesner, L; Chaisson, RE, McIlleron, H. Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis co-infection. Journal of Infectious Diseases (2015) 211: 197-205. PMC4334832.
McIlleron, H; Denti, P; Cohn, S; Mashabela, F; Hoffmann, J; Shembe, S; Msandiwa, R; Wiesner, L; Velaphi, S; Lala, S; Chaisson, R; Martinson, N; Dooley, KE. Prevention of tuberculosis using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants. Journal of Antimicrobial Chemotherapy (2017) 72: 2028-2034. PMC5890683.
Mathad JS, Savic R, Britto P, Jayachandran P, Wiesner L, Montepiedra G, Norman J, Zhang N, Townely E, Chakhtoura N, Bradford S, Patil S, Popson S, Chipato T, Rouzier V, Langat D, Chalermchockcharoentkit A, Kamthunzi P, Gupta A, Dooley KE: IMPAACT 2001 Study Team. Pharmacokinetics and safety of three months of weekly rifapentine and isoniazid for tuberculosis prevention in pregnant women. Clin Inf Dis, in press.
Paradkar, MS; D, BD; Mvalo, T; Arenivas, A; Thakur, KT; Wolf, L; Nimkar, S; Inamdar, S; Giridharan, P; Selladurai, E; Kinikar, A; Valvi, C; Khwaja, S; Gadama, D; Balaji, S; Kattagoni, KY; Venkatesan, M; Savic, R; Swaminathan, S; Gupta, A; Gupte, N; Mave, V; Dooley KE; for the TBM-KIDS Study Team. Randomized clinical trial of high dose rifampicin with or without levofloxacin versus standard of care for paediatric tuberculous meningitis: the TBM-KIDS Trial. Clin Inf Dis, in press.